Receptive sites on postsynaptic membranes are thought to be the key to specificity in chemical neurotransmission. We propose to study the high affinity, low capacity binding site or receptor for gamma- aminobutyric acid (GABA). Synaptic plasma membranes (SPM) will be prepared from synaptosomes or nerve ending particles of rat and bovine cerebellar cortex. Rapid and sensitive assays of reversible ligand binding will be employed to determine the specific, high affinity GABA binding site in SPM. In addition, the GABA receptor will be solubilized from SPM using non-ionic detergents and/or organic solvent extraction. The interaction of putative agonists and antagonists of GABA with SPM and solubilized fractions of SPM will be examined. The solubilized GABA receptor will be purified via gel filtration, ion exchange, and/or affinity chromatography and characterized with respect to its chemical and physical properties. Long-range goals of this research include mechanistic studies of the receptor employing artificial membranes and the preparation of antibodies to the receptor for use in the immunohistochemical localization of the receptor as well as for the development of a complement fixation assay for the presence of receptor.